Our group has previously identified several molecular alterations underlying neuroplasticity in brain regions implicated in depression. Ongoing studies indicate that many of these molecular and cellular changes can be related to functional alterations in behavioral models of depression and/or antidepressant response behaviors as well as related behaviors such as anxiety. The purpose of the Behavioral Core is to provide standardized paradigms that can be used by several of the Projects in this application. Behavioral studies will be performed in animals in which a protein or factor of interest will be modulated by one of several techniques including: (1) genetic mutations that increase or decrease gene expression in mice: The transgenic mice to be tested include those with inducible and region-specific transgene expression and constitutive and conditional null mutant mice (see Molecular and Transgenic Core), (2) direct transfections with viral vectors resulting in over-expression of a protein of interest, and (3) intracerebral infusions of pharmacological agents such as activators or inhibitors of proteins of interest. Thus, the Behavioral Core will provide support that is complementary to the Molecular and Transgenic Core. Behavioral studies will also be performed in animals which have been exposed to chronic stress paradigms or in which estrogen function has been modified as part of the aim of assessing a role of estrogen in depression. The Behavioral Core will provide the following behavioral models and treatments: I. Models of depression/antidepressant responsive behaviors; II. Models of anxiety and conditioned fear; III. Characterization of activity and stimulus sensitivity; IV. Exposure to stress or enrichment paradigms and estrogen treatment. These behavioral models and treatment paradigms will be available to the investigators of the individual Projects. The behavioral paradigms included in this Core represent the most widely used behavioral procedures relevant to the research projects of this grant. The consolidation of these methodologies in the Core assures that all investigators of the projects will have access to established behavioral paradigms, and that the use of standard, rigorous methodologies will be consistent across all of the projects comprising the program. In some cases, results generated by the Core will provide impetus for further assessment in additional more specific and/or complex paradigms that are included in the individual projects (i.e., Projects 4). The organization of the Core facilitates comparison of behavioral findings between projects and enhances our ability to integrate molecular, cellular, and behavioral levels of analyses.